Abstract：
OBJECTIVE: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats.
METHODS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max).
RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 μg/mL (0.45-1.17 μg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91-2.48 μg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose.
CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.
METHODS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max).
RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 μg/mL (0.45-1.17 μg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91-2.48 μg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose.
CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.
摘要：
目的：本研究的目的是描述索他洛尔在健康猫中的单剂量和多剂量药代动力学和尿消除。
方法：六只成年目的饲养的猫材料和方法：在一项随机交叉研究中，以单次静脉推注和单次口服剂量给猫服用2mg索他洛尔/kg体重，为期2周。然后,相同的猫每12小时口服3mg索他洛尔/kg,持续2周。在给药后48小时的预定时间点收集血液样品，以使用超高压液相色谱和质谱法定量索他洛尔。非房室分析用于获得药代动力学参数。数据表示为中值(min-max)。
结果：静脉注射后，血浆清除率和分布体积分别为9.22mL/min/kg（5.69-10.89）和2175.56（1961-2341.57）mL/kg，分别。在单次口服剂量后,生物利用度为88.41%(62.75-130.29)。单次口服剂量（2mg/kg）后，血浆峰值浓度（Cmax）和达到Cmax的时间为0.94μg/mL（0.45-1.17）和1.5h（0.5-4），和2.29μg/mL（1.91-2.48）和1.0h（0.5-1.5）与长期口服给药（3mg/kg），分别。单次和长期口服给药的消除半衰期为2.75h（2.52-4.10）和4.29h（3.33-5.53），分别。长期给药后积累指数为1.17（1.09-1.29）。尿索他洛尔的回收率为静脉内剂量的81-108％。
结论：口服索他洛尔导致在其他物种中有效的血浆浓度，具有良好至优异的口服生物利用度。尿液排泄似乎是消除的主要途径。反复口服给药后，估计最小的药物积累。由于非线性动力学的可能性，建议在猫中进行其他研究。
方法：六只成年目的饲养的猫材料和方法：在一项随机交叉研究中，以单次静脉推注和单次口服剂量给猫服用2mg索他洛尔/kg体重，为期2周。然后,相同的猫每12小时口服3mg索他洛尔/kg,持续2周。在给药后48小时的预定时间点收集血液样品，以使用超高压液相色谱和质谱法定量索他洛尔。非房室分析用于获得药代动力学参数。数据表示为中值(min-max)。
结果：静脉注射后，血浆清除率和分布体积分别为9.22mL/min/kg（5.69-10.89）和2175.56（1961-2341.57）mL/kg，分别。在单次口服剂量后,生物利用度为88.41%(62.75-130.29)。单次口服剂量（2mg/kg）后，血浆峰值浓度（Cmax）和达到Cmax的时间为0.94μg/mL（0.45-1.17）和1.5h（0.5-4），和2.29μg/mL（1.91-2.48）和1.0h（0.5-1.5）与长期口服给药（3mg/kg），分别。单次和长期口服给药的消除半衰期为2.75h（2.52-4.10）和4.29h（3.33-5.53），分别。长期给药后积累指数为1.17（1.09-1.29）。尿索他洛尔的回收率为静脉内剂量的81-108％。
结论：口服索他洛尔导致在其他物种中有效的血浆浓度，具有良好至优异的口服生物利用度。尿液排泄似乎是消除的主要途径。反复口服给药后，估计最小的药物积累。由于非线性动力学的可能性，建议在猫中进行其他研究。
